Stimulation of endogenous ADP-ribosylation by brefeldin A

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 91; no. 3; pp. 1114 - 1118
• Main Authors: De Matteis, M A, Di Girolamo, M, Colanzi, A, Pallas, M, Di Tullio, G, McDonald, L J, Moss, J, Santini, G, Bannykh, S, Corda, D
• Format: Journal Article
• Language: English
• Published: United States National Acad Sciences 01.02.1994; National Academy of Sciences
• Subjects: Adenosine Diphosphate Ribose - metabolism; ADP Ribose Transferases; ADP-Ribosylation Factors; Animals; Biological Transport, Active; Brefeldin A; Cell Line; Cellular biology; Cyclopentanes - pharmacology; Fungi; Glyceraldehyde-3-Phosphate Dehydrogenases - metabolism; GTP-Binding Proteins - metabolism; Membranes; Mycotoxins - pharmacology; NAD - metabolism; Poly(ADP-ribose) Polymerases - metabolism; Proteins - metabolism; Rats; Substrate Specificity
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.91.3.1114

Brefeldin A (BFA) is a fungal metabolite that exerts profound and generally inhibitory actions on membrane transport. At least some of the BFA effects are due to inhibition of the GDP-GTP exchange on the ADP-ribosylation factor (ARF) catalyzed by membrane protein(s). ARF activation is likely to be a key event in the association of non-clathrin coat components, including ARF itself, onto transport organelles. ARF, in addition to participating in membrane transport, is known to function as a cofactor in the enzymatic activity of cholera toxin, a bacterial ADP-ribosyltransferase. In this study we have examined whether BFA, in addition to inhibiting membrane transport, might affect endogenous ADP-ribosylation in eukaryotic cells. Two cytosolic proteins of 38 and 50 kDa were enzymatically ADP-ribosylated in the presence of BFA in cellular extracts. The 38-kDa substrate was tentatively identified as the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase. The BFA-binding components mediating inhibition of membrane traffic and stimulation of ADP-ribosylation appear to have the same ligand specificity. These data demonstrate the existence of a BFA-sensitive mono(ADP-ribosyl)transferase that may play a role in membrane movements.